Comparative Transcriptome Analysis Provides Insights into the Molecular Mechanism Underlying the Effect of MeJA Treatment on the Biosynthesis of Saikosaponins in Bupleurum chinense DC.

Bupleurum chinense DC. is a well-known traditional Chinese medicinal plant that produces saikosaponins (SSs), which possess hepatoprotective, antipyretic, and anti-inflammatory activities. Methyl jasmonate (MeJA) is a signalling phytohormone that can increase the accumulation of SSs in the root of Bupleurum plants. However, the molecular understanding of MeJA-mediated SS biosynthesis is not clear. Therefore, it is necessary to explore the molecular mechanism underlying the response of B. chinense DC. to MeJA in roots. In this study, we performed comparative transcriptome analysis of B. chinense DC. roots with different MeJA treatment times. In total, 104,057 unigenes were identified, of which 4053 were differentially expressed genes (DEGs). Most of the DEGs were downregulated after MeJA treatment, and GO enrichment analysis showed that they were mainly related to biological processes involved in stress responses and development. A total of 88 DEGs encoding enzymes known to be involved in the SS synthesis pathway were found, and most were significantly downregulated within 24 h. Based on the DEGs, 99 transcription factors (TFs) belonging to the AP2/ERF, WRKY, bZIP, ZFP, and bHLH families with different expression patterns were also identified. Further integrated analysis indicated that 20 DEGs involved in the SS synthesis pathway and 12 DEGs encoding TFs presented strong correlations with the SS contents, and these DEGs may be critical for the biosynthesis and regulation of SSs. These findings will be critical for further study of the response of B. chinense DC. to MeJA for SS biosynthesis.

Molecular cloning, functional characterization and expression of the ß-amyrin synthase gene involved in saikosaponin biosynthesis in Bupleurum chinense DC.

Bupleurum chinense DC. is a commonly used plant in traditional Chinese medicine, and saikosaponins(SSs) are the main active oleanane-typetriterpene saponins in B. chinense. ß-Amyrin synthase (ß-AS) is an important enzyme in oleanane-type triterpenoid saponin synthesis, but its role in saikosaponin synthesis has rarely been studied. Here, the putative ß-AS gene BcBAS1(Accession No.ON890382) selected according to metabolomic and transcriptomic analyses was cloned and functionally characterized by heterologous expression in Escherichia coli and Pichia pastoris, and its subcellular localization and expression patterns were examined. The molecular weight of the BcBAS1 recombinant protein was approximately 87 kDa, and this protein could catalyse the production of ß-amyrin, the precursor of SSs. Furthermore, BcBAS1 was located in the cytosol, and relative expression in four tissues of the four genotypes was positively correlated with SSa and SSd contents. Our results indicate that BcBAS1 is a ß-AS gene and may play an important role in saikosaponin biosynthesis and regulation. This study sheds light on the role of ß-AS genes in the synthesis of SSs and provides insights for the metabolic engineering of SSs.

Transcriptome Level Reveals the Triterpenoid Saponin Biosynthesis Pathway of Bupleurum falcatum L.

Bupleurum falcatum L. is frequently used in traditional herbal medicine in Asia. Saikosaponins (SSs) are the main bioactive ingredients of B. falcatum, but the biosynthetic pathway of SSs is unclear, and the biosynthesis of species-specific phytometabolites is little known. Here we resolved the transcriptome profiles of B. falcatum to identify candidate genes that might be involved in the biosynthesis of SSs. By isoform sequencing (Iso-Seq) analyses of the whole plant, a total of 26.98 Gb of nucleotides were obtained and 124,188 unigenes were identified, and 81,594 unigenes were successfully annotated. A total of 1033 unigenes of 20 families related to the mevalonate (MVA) pathway and methylerythritol phosphate (MEP) pathway of the SS biosynthetic pathway were identified. The WGCNA (weighted gene co-expression network analysis) of these unigenes revealed that only the co-expression module of MEmagenta, which contained 343 unigenes, was highly correlated with the biosynthesis of SSs. Comparing differentially expressed gene analysis and the WGCNA indicated that 130 out of 343 genes of the MEmagenta module exhibited differential expression levels, and genes with the most "hubness" within this module were predicted. Manipulation of these genes might improve the biosynthesis of SSs.

Evaluation of the National Comprehensive Cancer Network and European Society for Medical Oncology Nasopharyngeal Carcinoma Surveillance Guidelines.

Purpose: The National Comprehensive Cancer Network (NCCN) and European Society for Medical Oncology (ESMO) provide surveillance guidelines for nasopharyngeal carcinoma (NPC). We evaluated the ability of these guidelines to capture disease recurrence. Materials and methods: All 749 NPC patients were stratified for analysis by T and N stage. We evaluated the guidelines by calculating the percentage of relapses detected when following the 2018 NCCN, 2015 NCCN, and 2012 ESMO surveillance guidelines, and related surveillance costs were compared. Results: At a median follow-up of 100.8 months, 168 patients (22.4%) had experienced recurrence. Nineteen recurrences (11.3%) were detected using the 2018 NCCN, 53 (31.5%) using the 2015 NCCN and 46 (27.4%) using the ESMO guidelines. To capture 95% recurrences, surveillance would be required for 85.57 months for T1/2, 67.45 months for T3/4, 83.57 months for N0/1, and 55.80 months for N2/3 disease. In T1/2 disease, Medicare surveillance costs per patient were US$1642.66 using 2018 NCCN or ESMO and US$2179.81 using 2015 NCCN. Costs per recurrence detected were US$42,578.64, 62,088.70, and 73,329.76 using 2018 NCCN, 2015 NCCN, and ESMO, respectively. Conclusions: If strictly followed, the NCCN and ESMO guidelines will miss more than two-thirds recurrences. Improved surveillance algorithms to balance patient benefit against costs are needed.

[Effect of Qingshen Granules on inflammation/hepcidin axis and iron metabolism in patients with renal anemia: a single-center, randomized controlled trial].

OBJECTIVE: To evaluate the therapeutic effect of Qingshen Granules on renal anemia in patients with damp-heat syndrome and explore the mechanisms in light of inflammation/hepcidin axis and iron metabolism. METHODS: Sixty patients with renal anemia and dampness-heat syndrome were randomized into control group (n=30) and treatment group (n=30). All the patients were given routine treatment, and the patients in the treatment group received additional treatment with Qingshen Granules (3 times a day). After 12 weeks of treatments, the patients were examined for changes in the integral value of TCM syndrome, serum creatinine (Scr), glomerular filtration rate (eGFR), hemoglobin (HGB), hematocrit (HCT), red blood cell (RBC) count, interleukin-6 (IL-6), hypersensitive C-reactive protein (hs-CRP), ferritin, growth differentiation factor-15 (GDF-15), serum iron (SI), total iron binding capacity (TIBC), transferrin saturation (TAST), soluble transferrin receptor (sTfR) and ferritin levels. RESULTS: After the treatment, the scores of TCM syndrome were significantly improved in the treatment group and were better than those in the control group (P=0.000). Scr and eGFR were improved in both groups after the treatment. The levels of HGB, HCT and RBC were all improved in the two groups after treatment, and the improvements were more obvious in the treatment group (P=0.002, 0.002, and 0.017, respectively). The levels of IL-6, hs-CRP, hepcidine and GDF-15 were all lowered in the two groups after the treatment, and they were all significantly lower in the treatment group than in the control group (all P=0.000). The treatments increased the levels of SI and TAST in both of the groups, and compared with those in control group, the levels of TIBC, sTfR and ferritin were significantly lowered in the treatment group after the 12-week treatment (P=0.000). CONCLUSIONS: Qingshen granules can effectively improve renal anemia in patients with damp-heat syndrome possibly by improving iron metabolism through alleviation of inflammation and reduction of hepcidine level.

Investigation on polyphosphate accumulation in the sulfur transformation-centric EBPR (SEBPR) process for treatment of high-temperature saline wastewater.

This study investigated the polyphosphates accumulation rate in a novel sulfur transformation-centric enhanced biological phosphorus removal (SEBPR) process. The SEBPR system was continuously operated over 120 days in a sequencing batch reactor (SBR) that alternated between the anaerobic mode and the anoxic mode of operation (temperature: 30 °C and salinity: 6000 mg/L Cl-). In addition to the SBR, batch experiments were carried out to test the effect of two different sulfate concentrations on the system performance and sulfur-phosphorus transformations. The key intercellular polymers of polyphosphates and polysulfur (poly-S) were identified by employing advanced microscopes. Metagenomic analysis was performed to characterize the diversity of microbes and their functions enriched in the SEBPR system. Finally, several molecular techniques including flow cytometry cell sorting and 16S DNA high-throughput sequencing were applied to identify the phosphorus-accumulating organisms (PAOs). The amounts of P release and P uptake in the SEBPR increased gradually to nearly 18 ±â€¯6.4 mg P/L and 26.5 ±â€¯6.7 mg P/L respectively, yielding a net P removal efficiency of 84 ±â€¯25%. Batch tests indicated no polyhydroxyalkanate (PHA) synthesis, but P uptake was observed and it was correlated with the intracellular poly-S consumption, suggesting that the poly-S could act as an intracellular energy source for P uptake and polyphosphates formation. Moreover, CLSM and TEM micrographs clearly showed the presence of intercellular polyphosphates and poly-S respectively. Metagenomic analysis revealed that Proteobacteria (36.5%), Bacteroidetes (23.3%), Thermotogae (7.1%), Chloroflexi (4.5%) and Firmicutes (2.3%) were the dominant phyla in Bacteria. The conventional PAO of Candidatus Accumulibacter was found at a low abundance of 0.32% only; and an uncultured genus close to Rhodobacteraceae at the family level is speculated to be the putative sulfur PAO (SPAO). Finally, this research suggests that poly-S considerably impacts on polyphosphates accumulation in the SEBPR system when no PHAs are formed.

Multiple-cycle operation of sulphur-cycle-enhanced biological phosphorus removal to maintain stable performance at high temperatures.

This study investigated a new method of multiple-cycle operation of a sulphur-cycle-enhanced biological phosphorus (P) removal system to maintain good phosphorus removal performance at a high temperature (30 °C). The findings demonstrate that P removal was low and unstable under a normal cycle (77 ±â€¯18%), but multiple cycles resulted in a high and quite stable level of P removal (88 ±â€¯9%). Moreover, in the normal mode, the polyhydroxyalkanoate levels increased significantly from 2 to 15 mg C/g of VSS, the glycogen level doubled from 5 to 10 mg C/g of VSS and the polyhydroxyalkanoate and glycogen levels were maintained at considerably low levels after multiple cycles (only 5 C/g of VSS). The 16S rRNA high-throughput sequencing analysis revealed that the genera Thioalbus and Psychrobacter in the gamma-Proteobacteria class were the key functional communities. These findings suggest a high level of P removal with multiple cycles of sulphur-cycle enhanced biological phosphorus removal.

Genome-centric metagenomics resolves microbial diversity and prevalent truncated denitrification pathways in a denitrifying PAO-enriched bioprocess.

Denitrification is the stepwise microbial reduction of nitrate or nitrite (NO2-) to nitrogen gas via the obligate intermediates nitric oxide (NO) and nitrous oxide (N2O). Substantial N2O accumulation has been reported in denitrifying enhanced biological phosphorus removal (EBPR) bioreactors enriched in denitrifying polyphosphate accumulating organisms (DPAOs), but little is known about underlying mechanisms for N2O generation, prevalence of complete versus truncated denitrification pathways, or the impact of NO2- feed on DPAO-enriched consortia. To address this knowledge gap, we employed genome-resolved metagenomics to investigate nitrogen transformation potential in a NO2- fed denitrifying EBPR bioreactor enriched in Candidatus Accumulibacter and prone to N2O accumulation. Our analysis yielded 41 near-complete metagenome-assembled genomes (MAGs), including two co-occurring Accumulibacter strains affiliated with clades IA and IC (the first published genome from this clade) and 39 non-PAO flanking bacterial genomes. The dominant Accumulibacter clade IA encoded genes for complete denitrification, while the lower abundance Accumulibacter clade IC harbored all denitrification genes except for a canonical respiratory NO reductase. Analysis of the 39 non-PAO MAGs revealed a high prevalence of taxa harboring an incomplete denitrification pathway. Of the 27 MAGs harboring capacity for at least one step in the denitrification pathway, 10 were putative N2O producers lacking N2O reductase, 16 were putative N2O reducers that lacked at least one upstream denitrification gene, and only one harbored a complete denitrification pathway. We also documented increasing abundance over the course of reactor operation of putative N2O producers. Our results suggest that the unusually high levels of N2O production observed in this Accumulibacter-enriched consortium are linked in part to the selection for non-PAO flanking microorganisms with truncated denitrification pathways.

Evidence Underlying Recommendations and Payments from Industry to Authors of the National Comprehensive Cancer Network Guidelines.

BACKGROUND: The National Comprehensive Cancer Network (NCCN) guidelines are among the most widely used guidance in oncology. It is critical to understand the extent to which the recommendations in these guidelines are supported by evidence and to investigate whether these recommendations have been influenced by payments from industry to authors. MATERIALS AND METHODS: We examined the quality and consistency of evidence, as scored by guidelines authors, for systemic treatment incorporated in the NCCN guidelines. Payments data in 2015 were manually abstracted using the Open Payments database, which discloses all payments between the industry and American physicians. Correlations between the percentage of authors who received payments and the proportion of recommendations developed from low-level evidence per guideline were calculated using Spearman rank correlation. RESULTS: In total, 1,782 recommendations were identified in 29 guidelines, of which 1,282 (71.9%) were based on low-quality or low-consistency evidence (low-level evidence), including "case reports or clinical experience only" (18.9%). A substantial proportion (31/143, 21.7%) of category 1 (the highest level) recommendations were based on low-level evidence. The majority of authors (87.1%) received payments from industry. However, no association was found between the prevalence of payments among authors and the percentage of recommendations developed from low-level evidence per guideline. CONCLUSION: The majority of systemic treatment recommendations in the NCCN guidelines are based on low-level evidence, including more than one in five category 1 recommendations. Payments from industry were prevalent among authors. However, industrial payments among authors were not associated with inclusion of regimen/agent for which there is no conclusive evidence in the guidelines. IMPLICATIONS FOR PRACTICE: The authors found that the majority (71.9%) of systemic treatment recommendations issued in the current National Comprehensive Cancer Network guidelines were based on low-level evidence. Physicians should remain cautious when using current guidelines as the sole source guiding patient care decisions.

[Effect of Ronghuang Granule on serum FGF23, FGFRs and Klotho in non-dialysis patients with CKD-MBD and kidney deficiency and damp-heat syndrome].

OBJECTIVE: To observe the effect of Ronghuang granule on serum fibroblast growth factor 23 (FGF23), fibroblast growth factor receptor (FGFRs) and Klotho protein levels in non-dialysis patients with chronic kidney disease-mineral and bone disorder (CKD-MBD) and kidney deficiency and damp heat syndrome. METHODS: Seventy non-dialysis CKD-MBD patients with kidney deficiency and dampness-heat syndrome were randomized into control group (n=35) and treatment group (n=35). All the patients were given routine treatment combined with traditional Chinese medicine retention enema, and the patients in the treatment group received additional Ronghuang granule treatment (3 times a day). After the 12-week treatments, the patients were examined for changes of TCM syndromes. Serum levels of Ca, P, parathyroid hormone (iPTH), FGF23, FGFRs and Klotho proteins were detected before and after treatment. These parameters were also examined in 20 healthy volunteers. RESULTS: Sixty-five patients completed the study, including 33 in the control group and 32 in the treatment group. The patients in the treatment group showed significantly better treatment responses than those in the control group (P < 0.05 or 0.01). At 4, 8, and 12 weeks of treatment, the patients in the treatment group had significantly lowered scores of TCM syndromes compared with the score before treatment (P < 0.05 or 0.01), while in the control group, significant reduction of the scores occurred only at 12 weeks (P < 0.05); at each of the time points, the treatment group had significantly greater reductions in the score than the control group (P < 0.01). Significant improvements in serum Ca, P and iPTH levels were observed at 4, 8, and 12 weeks in the treatment group (P < 0.05) but only at 12 weeks in the control group (P < 0.05). The patients in the control and treatment groups all showed elevated serum levels of FGF23, FGFRs and Klotho protein compared with the normal subjects (P < 0.01); FGF23, FGFRs and Klotho levels were significantly reduced in the treatment group (P < 0.05) but remained unchanged in the control group (P>0.05), showing significant differences between the two groups. CONCLUSIONS: Ronghuang granule improves the clinical symptoms of non-dialysis CKD-MBD patients with kidney deficiency and dampness heat syndrome by reducing serum levels of FGF23, FGFRs and Klotho, improving calcium and phosphorus metabolism disorder, and inhibiting secondary hyperparathyroidism.

A network meta-analysis in comparing prophylactic treatments of radiotherapy-induced oral mucositis for patients with head and neck cancers receiving radiotherapy.

OBJECTIVES: The objective of this network meta-analysis is to optimize the prophylactic treatment for radiotherapy-induced oral mucositis in patients with head and neck cancer (HNSCC) receiving postoperative or definitive radiotherapy with or without chemotherapy. MATERIALS AND METHODS: We searched electronic databases to identify all eligible randomized clinical trials on oral mucositis. The endpoint was grade 0-2 oral mucositis. Odds ratios (OR) and the corresponding 95% confidence intervals (CI) were extracted. Network meta-analysis was performed using the frequentist approach to conduct multiple treatment comparisons. RESULTS: In total, 57 trials with 5261 patients were eligible for this study. Both direct and network meta-analysis revealed that low-level laser additional to standard oral care (SOC) was better than most of the other treatments and achieved the highest effect on grade 0-2 oral mucositis, with a surface under the cumulative ranking curve (SUCRA) of 95.8%; however, SOC with or without placebo had worse effect than most of the other treatments and was ranked worst (SUCRA = 0.4%). Moreover, sensitivity analysis performed after we had combined the SOC and placebo groups (non-medication treatment, NMT) yielded similar results, with SUCRA of 91.3% and 3.5% for low-level laser and NMT, respectively. CONCLUSIONS: Low-level laser additional to SOC may be a more effective prophylactic treatment for reducing severe radiotherapy-induced oral mucositis; SOC alone is insufficient for patients with HNSCC receiving postoperative or definitive radiotherapy with or without chemotherapy.

Refining the Role of Lymph Node Biopsy in Survival for Patients with Nasopharyngeal Carcinoma: Population-Based Study from the Surveillance Epidemiology and End-Results Registry.

BACKGROUND: The updated version of the National Comprehensive Cancer Network (NCCN) guidelines revised pretreatment workup for nasopharyngeal carcinoma (NPC) into "biopsy of the primary site or neck." Despite provision of important diagnostic information, concerns regarding tumor cell dissemination limit the application of lymph node biopsy. This study aimed to investigate whether biopsy of the neck is associated with impaired survival in NPC. METHODS: A propensity score-matched, population-based cohort identified from the Surveillance, Epidemiology, and End Results database was used to compare overall survival (OS) and disease-specific survival (DSS) of patients who underwent pretreatment cervical lymph node biopsy without subsequent neck dissection or removal of node compared with patients who did not undergo node biopsy. RESULTS: Of 2910 eligible patients, 416 (14.3%) underwent pretreatment lymph node biopsy. After use of control for patient, tumor, and demographic characteristics, biopsy was not associated with impaired OS (hazard ratio [HR], 1.15; 95% confidence interval [CI] 0.89-1.47; P = 0.29) or DSS (HR, 1.07; 95% CI 0.81-1.40; P = 0.63). Interestingly, in the subgroup analysis, the unfavorable effect of biopsy was observed for patients with differentiated non-keratinizing squamous cell carcinoma (but not other histologic types). Race did not positively alter the survival outcomes. CONCLUSIONS: The findings provide reference for clinical practice, showing that pretreatment cervical lymph node biopsy is not associated with impaired survival in NPC, except for patients with differentiated non-keratinizing squamous cell carcinoma. The recommended NCCN guidelines would be more specific by adding details to the general recommendation that neck biopsy is safe for all patients. Future prospective studies are needed to verify the study findings.

Adjuvant chemotherapy in patients with locoregionally advanced nasopharyngeal carcinoma: Long-term results of a phase 3 multicentre randomised controlled trial.

AIM OF THE STUDY: Previous results from our trial showed that adjuvant cisplatin and fluorouracil chemotherapy did not significantly improve survival after concurrent chemoradiotherapy (CCRT) in locoregionally advanced nasopharyngeal carcinoma (NPC) at 2 years. Here, we present the data of long-term survival and late toxicities to further assess the ultimate therapeutic index of adjuvant chemotherapy (AC). METHODS: Patients with stage III-IVB (except T3-4N0) NPC were randomly assigned to receive CCRT plus AC or CCRT only at seven institutions in China. Patients in both groups received cisplatin 40 mg/m2 weekly up to 7 weeks concurrently with radiotherapy. The CCRT plus AC group subsequently received adjuvant cisplatin 80 mg/m2 and fluorouracil 800 mg/m2/d for 120 h every 4 weeks for three cycles. The primary end-point was failure-free survival. RESULTS: Two hundred and fifty-one patients were randomised to the CCRT plus AC group and 257 to the CCRT only group. After a median follow-up of 68.4 months, estimated 5-year failure-free survival rate was 75% in the CCRT plus AC group and 71% in the CCRT only group (hazard ratio 0.88, 95% confidence interval 0.64-1.22; p = 0.45). 66 (27%) of 249 patients in the CCRT plus AC group and 53 (21%) of 254 patients in the CCRT only group developed one or more late grade 3-4 toxicities (p = 0.14). CONCLUSION: Adjuvant cisplatin and fluorouracil chemotherapy still failed to demonstrate significant survival benefit after CCRT in locoregionally advanced NPC based on the long-term follow-up data, and addition of adjuvant cisplatin and fluorouracil did not significantly increase late toxicities. REGISTRATION NUMBER: NCT00677118.

Exploring the Shift in Structure and Function of Microbial Communities Performing Biological Phosphorus Removal.

A sequencing batch reactor fed mainly by acetate was operated to perform enhanced biological phosphorus removal (EBPR). A short-term pH shock from 7.0 to 6.0 led to a complete loss of phosphate-removing capability and a drastic change of microbial communities. 16S rRNA gene pyrosequencing showed that large proportions of glycogen accumulating organisms (GAOs) (accounted for 16% of bacteria) bloomed, including Candidatus Competibacter phosphatis and Defluviicoccus-related tetrad-forming organism, causing deteriorated EBPR performance. The EBPR performance recovered with time and the dominant Candidatus Accumulibacter (Accumulibacter) clades shifted from Clade IIC to IIA while GAOs populations shrank significantly. The Accumulibacter population variation provided a good opportunity for genome binning using a bi-dimensional coverage method, and a genome of Accumulibacter Clade IIC was well retrieved with over 90% completeness. Comparative genomic analysis demonstrated that Accumulibacter clades had different abilities in nitrogen metabolism and carbon fixation, which shed light on enriching different Accumulibacter populations selectively.

[Intervention of Qingshen Granule for Immune Inflammation of Chronic Renal Failure Patients with Damp-heat Syndrome].

Objective To observe the effect of Qingshen Granule (QG) on the immune function of chronic renal failure (CRF) patients with damp-heat syndrome (DHS). Methods A total of 162 CRF patients were assigned to the treated group and the control group by random digit table, 81 in each group. All patients were treated with conventional Western medical therapy. Those in the treated group addition- ally took QG, one package each time (10 g) , thrice per day. The therapeutic course for all was 12 weeks. The clinical efficacy was observed in the two groups. The contents of peripheral blood CD4 ⁺ T cells, CD8 ⁺ T cells, Thl7 cells, and nuclear factor-κB p65 (NF-κBp65) activity were detected using flow cy- tometry. Expressions of serum IL-17, tumor necrosis factor receptor-associated factor 6 (TRAF6), ma- trix metalloproteinase-9 (MMP-9) , matrix metalloproteinase inhibitor-I (TIMP-1 ) , collagen N (Col-V) were detected using ELISA. Results Finally 156 patients completed the trial (77 cases in the treated group and 79 cases in the control group). The total clinical curative effective rate was significantly higher in the treated group (80. 52%, 62/77) than in the control group (68. 35%, 54/79) with statistical differ- ences between the two groups (x² = 54. 849, P <0. 05). Compared with before treatment in the same group, the levels of peripheral blood CD4 ⁺ /CD8 ⁺ , Thl7 cell content, NF-κB p65 activity, serum levels of IL-17, TRAF6, and TIMP-1 , TIMP-1/MMP-9 ratio, Col-IV level all decreased in the treated group after treat- ment (P <0. 05) ; serum MMP-9 level decreased .(P <0. 05) and TIMP-1 /MMP-9 ratio increased (P <0. 05) in the control group. Compared with the control group, CD4⁺/CD8 ⁺ T cell ratio, Th17 cell content, NF-κB p65 activity decreased more obviously in the treated group after treatment (P <0. 05). Serum levels of IL- 17, TRAF6, TIMP-1, TIMP-1/MMP-9 ratio, and Col-IV all decreased (P <0.05) and MMP-9 level increased (P <0. 05) in the treated group (P <0. 05). Conclusion QG could adjust immune dysfunction and disar- ranged immunity mediated inflammatory response, and attenuate renal fibrosis in CKD patients with DHS.

Genome reconstruction and gene expression of "Candidatus Accumulibacter phosphatis" Clade IB performing biological phosphorus removal.

We report the first integrated metatranscriptomic and metagenomic analysis of enhanced biological phosphorus removal (EBPR) sludge. A draft genome of Candidatus Accumulibacter spp. strain HKU-1, a member of Clade IB, was retrieved. It was estimated to be ∼90% complete and shared average nucleotide identities of 83% and 88% with the finished genome CAP IIA UW-1 and the draft genome CAP IA UW-2, respectively. Different from CAP IIA UW-1, the phosphotransferase (pap) in polyphosphate metabolism and V-ATPase in orthophosphate transport were absent from CAP IB HKU-1. Additionally, unlike CAP IA UW-2, CAP IB HKU-1 carried the genes for carbon fixation and nitrogen fixation. Despite these differences, the key genes required for acetate uptake, glycolysis and polyhydroxyalkanoate (PHA) synthesis were conserved in all these Accumulibacter genomes. The preliminary metatranscriptomic results revealed that the most significantly up-regulated genes of CAP IB HKU-1 from the anaerobic to the aerobic phase were responsible for assimilatory sulfate reduction, genetic information processing and phosphorus absorption, while the down-regulated genes were related to N2O reduction, PHA synthesis and acetyl-CoA formation. This study yielded another important Accumulibacter genome, revealed the functional difference within the Accumulibacter Type I, and uncovered the genetic responses to EBPR stimuli at a higher resolution.

Progress report of a randomized trial comparing long-term survival and late toxicity of concurrent chemoradiotherapy with adjuvant chemotherapy versus radiotherapy alone in patients with stage III to IVB nasopharyngeal carcinoma from endemic regions of China.

BACKGROUND: The objective of this study was to evaluate the long-term survival and late toxicities of concurrent-adjuvant chemotherapy in patients with stage III through IVB nasopharyngeal carcinoma (NPC) from endemic regions of China. METHODS: Patients with stage III to IVB NPC were assigned randomly to receive radiotherapy (RT) alone (the RT group) or RT plus concurrent adjuvant chemotherapy (the CRT group). CRT patients received concurrent cisplatin (40 mg/m2) weekly during RT followed by cisplatin (80 mg/m2) and fluorouracil (800 mg/m(2) daily for 5 days) every 4 weeks for 3 cycles. The primary endpoint was overall survival. RESULTS: In total, 316 patients underwent randomization, with 158 to each group. At a median follow-up of 70 months, the 5-year overall survival rate was 72% for the CRT group and 62% for the RT group (hazard ratio, 0.69; 95% confidence interval, 0.48-0.99; P = .043). Failure-free survival was significantly higher in the CRT group (P = .020). Most late toxicities were similar (33% vs. 26%; P = .089), except for cranial neuropathy (P = .042), peripheral neuropathy (P = .041), and ear damage (P = .048), which were significantly increased in the CRT group. CONCLUSIONS: The addition of concurrent adjuvant chemotherapy to RT provides survival benefits to patients with stage III through IVB NPC in endemic regions of China, and it does not increase most late toxicities apart from cranial neuropathy, peripheral neuropathy, and ear damage.

Concurrent chemoradiotherapy plus adjuvant chemotherapy versus concurrent chemoradiotherapy alone in patients with locoregionally advanced nasopharyngeal carcinoma: a phase 3 multicentre randomised controlled trial.

BACKGROUND: The effect of the addition of adjuvant chemotherapy to concurrent chemoradiotherapy in locoregionally advanced nasopharyngeal carcinoma is unclear. We aimed to assess the contribution of adjuvant chemotherapy to concurrent chemoradiotherapy versus concurrent chemoradiotherapy alone. METHODS: We did an open-label phase 3 multicentre randomised controlled trial at seven institutions in China. Randomisation was by a computer-generated random number code. Patients were stratified by treatment centre and randomly assigned in blocks of four. Treatment allocation was not masked. We randomly assigned patients with non-metastatic stage III or IV (except T3-4N0) nasopharyngeal carcinoma to receive concurrent chemoradiotherapy plus adjuvant chemotherapy or concurrent chemoradiotherapy alone. Patients in both groups received 40 mg/m(2) cisplatin weekly up to 7 weeks, concurrently with radiotherapy. Radiotherapy was given as 2·0-2·27 Gy per fraction with five daily fractions per week for 6-7 weeks to a total dose of 66 Gy or greater to the primary tumour and 60-66 Gy to the involved neck area. The concurrent chemoradiotherapy plus adjuvant chemotherapy group subsequently received 80 mg/m(2) adjuvant cisplatin and 800 mg/m(2) per day fluorouracil for 120 h every 4 weeks for three cycles. Our primary endpoint was failure-free survival. We did efficacy analyses in our intention-to-treat population. Our trial is ongoing; in this report we present the 2 year survival results and acute toxic effects. This trial is registered with ClinicalTrials.gov, number NCT00677118. FINDINGS: 251 patients were assigned to the concurrent chemoradiotherapy plus adjuvant chemotherapy group and 257 to the concurrent chemoradiotherapy alone group. After a median follow-up of 37·8 months (range 1·3-61·0), the estimated 2 year failure-free survival rate was 86% (95% CI 81-90) in the concurrent chemoradiotherapy plus adjuvant chemotherapy group and 84% (78-88) in concurrent chemoradiotherapy only group (hazard ratio 0·74, 95% CI 0·49-1·10; p=0·13). Stomatitis was the most commonly reported grade 3 or 4 adverse event during both radiotherapy (76 of 249 patients in the concurrent chemoradiotherapy plus adjuvant chemotherapy group and 82 of 254 in the concurrent chemoradiotherapy alone group) and adjuvant chemotherapy (43 [21%] of 205 patients treated with adjuvant chemotherapy). INTERPRETATION: Adjuvant cisplatin and fluorouracil chemotherapy did not significantly improve failure-free survival after concurrent chemoradiotherapy in locoregionally advanced nasopharyngeal carcinoma. Longer follow-up is needed to fully assess survival and late toxic effects, but such regimens should not, at present, be used outside well-designed clinical trials. FUNDING: Sun Yat-sen University Clinical Research 5010 Programme (No 2007037), Science Foundation of Key Hospital Clinical Programme of Ministry of Health PR China (No 2010-178), and Guangdong Province Universities and Colleges Pearl River Scholar Funded Scheme (2010).

Preliminary results of a prospective randomized trial comparing concurrent chemoradiotherapy plus adjuvant chemotherapy with radiotherapy alone in patients with locoregionally advanced nasopharyngeal carcinoma in endemic regions of china.

PURPOSE: A prospective randomized trial was performed to evaluate the efficacy of concurrent chemotherapy and adjuvant chemotherapy in patients with locoregionally advanced nasopharyngeal carcinoma (NPC) in endemic regions of China. METHODS AND MATERIALS: Between July 2002 and September 2005, 316 eligible patients were randomly assigned to receive either radiotherapy alone (RT) or chemoradiotherapy concurrent with adjuvant chemotherapy (CRT). All patients received 70 Gy in 7 weeks using standard RT portals and techniques. The CRT patients were given concurrent cisplatin (40 mg/m(2) on Day 1) weekly during RT, followed by cisplatin (80 mg/m(2) on Day 1) and fluorouracil (800 mg/m(2) on Days 1-5) every 4 weeks (Weeks 5, 9, and 13) for three cycles after completion of RT. All patients were analyzed by intent-to-treat analysis. RESULTS: The two groups were well-balanced in all prognostic factors and RT parameters. The CRT group experienced significantly more acute toxicity (62.6% vs. 32%, p = 0.000). A total of 107 patients (68%) and 97 patients (61%) completed all cycles of concurrent chemotherapy and adjuvant chemotherapy, with a median follow-up time of 29 months. The 2-year overall survival rate, failure-free survival rate, distant failure-free survival rate, and locoregional failure-free survival rate for the CRT and RT groups were 89.8% vs. 79.7% (p = 0.003), 84.6% vs. 72.5% (p = 0.001), 86.5% vs. 78.7% (p = 0.024), and 98.0% vs. 91.9% (p = 0.007), respectively. CONCLUSIONS: This trial demonstrated the significant survival benefits of concurrent chemotherapy plus adjuvant chemotherapy in patients with locoregionally advanced NPC in endemic regions of China.